Insect CncC: Roles in Redox Homeostasis, Physiology, and Insecticide Resistance, with Prospects for Biotechnological Applications

The Cap ‘n’ collar isoform C (CncC) transcription factor, the insect ortholog of mammalian nuclear factor erythroid 2-related factor 2 (Nrf2), serves as a central regulator of redox homeostasis and xenobiotic detoxification. Increasing evidence demonstrates that the functions of CncC extend beyond stress responses to include metamorphosis, immunity, reproduction, aging, and the development of metabolic insecticide resistance. In this review, we synthesize recent advances in insect CncC biology, with a focus on the conserved CncC/Keap1-ARE signaling pathway and its role in the detoxification of phytochemicals and insecticides. We further discuss insect-specific regulatory interactions between CncC and ecdysone signaling, as well as the gut microbiota, and compare insect CncC with mammalian Nrf2. From an applied perspective, we discuss CncC as a target for resistance management, including strategies involving RNAi and small-molecule inhibitors, its potential application in inducible bioreactors, and its value as a biomarker in environmental risk assessment. We conclude by identifying key open questions, including tissue-specific regulation, fitness costs of constitutive activation, and field relevance of CncC-mediated resistance, and highlight how addressing these gaps can support the development of sustainable pest control strategies.